Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
IntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage p...
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Frontiers Media S.A.
2022-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.892677/full |
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| author | Robert Wagner Robert Wagner Robert Wagner Robert Wagner Robert Wagner Sabine S. Eckstein Sabine S. Eckstein Louise Fritsche Louise Fritsche Katsiaryna Prystupa Katsiaryna Prystupa Katsiaryna Prystupa Sebastian Hörber Sebastian Hörber Sebastian Hörber Hans-Ulrich Häring Hans-Ulrich Häring Hans-Ulrich Häring Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas Peter Andreas Peter Andreas Peter Andreas Fritsche Andreas Fritsche Andreas Fritsche Martin Heni Martin Heni Martin Heni Martin Heni Martin Heni |
| author_facet | Robert Wagner Robert Wagner Robert Wagner Robert Wagner Robert Wagner Sabine S. Eckstein Sabine S. Eckstein Louise Fritsche Louise Fritsche Katsiaryna Prystupa Katsiaryna Prystupa Katsiaryna Prystupa Sebastian Hörber Sebastian Hörber Sebastian Hörber Hans-Ulrich Häring Hans-Ulrich Häring Hans-Ulrich Häring Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas Peter Andreas Peter Andreas Peter Andreas Fritsche Andreas Fritsche Andreas Fritsche Martin Heni Martin Heni Martin Heni Martin Heni Martin Heni |
| author_sort | Robert Wagner |
| collection | DOAJ |
| description | IntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health.Research Design and MethodsWe used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort.ResultsGlucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).ConclusionsGlucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype. |
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| last_indexed | 2024-04-13T21:30:10Z |
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| spelling | doaj.art-ef862a243d2141ab86ead8001b512cc52022-12-22T02:29:12ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.892677892677Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic HealthRobert Wagner0Robert Wagner1Robert Wagner2Robert Wagner3Robert Wagner4Sabine S. Eckstein5Sabine S. Eckstein6Louise Fritsche7Louise Fritsche8Katsiaryna Prystupa9Katsiaryna Prystupa10Katsiaryna Prystupa11Sebastian Hörber12Sebastian Hörber13Sebastian Hörber14Hans-Ulrich Häring15Hans-Ulrich Häring16Hans-Ulrich Häring17Andreas L. Birkenfeld18Andreas L. Birkenfeld19Andreas L. Birkenfeld20Andreas Peter21Andreas Peter22Andreas Peter23Andreas Fritsche24Andreas Fritsche25Andreas Fritsche26Martin Heni27Martin Heni28Martin Heni29Martin Heni30Martin Heni31Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyDepartment of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyGerman Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine IV, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, GermanyDivision of Endocrinology and Diabetology, Department of Internal Medicine 1, University Hospital Ulm, Ulm, GermanyIntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health.Research Design and MethodsWe used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort.ResultsGlucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).ConclusionsGlucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype.https://www.frontiersin.org/articles/10.3389/fendo.2022.892677/fullglucagonGlucagen-like peptidesinsulinmetabolismglicentin |
| spellingShingle | Robert Wagner Robert Wagner Robert Wagner Robert Wagner Robert Wagner Sabine S. Eckstein Sabine S. Eckstein Louise Fritsche Louise Fritsche Katsiaryna Prystupa Katsiaryna Prystupa Katsiaryna Prystupa Sebastian Hörber Sebastian Hörber Sebastian Hörber Hans-Ulrich Häring Hans-Ulrich Häring Hans-Ulrich Häring Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas L. Birkenfeld Andreas Peter Andreas Peter Andreas Peter Andreas Fritsche Andreas Fritsche Andreas Fritsche Martin Heni Martin Heni Martin Heni Martin Heni Martin Heni Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health Frontiers in Endocrinology glucagon Glucagen-like peptides insulin metabolism glicentin |
| title | Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health |
| title_full | Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health |
| title_fullStr | Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health |
| title_full_unstemmed | Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health |
| title_short | Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health |
| title_sort | postprandial dynamics of proglucagon cleavage products and their relation to metabolic health |
| topic | glucagon Glucagen-like peptides insulin metabolism glicentin |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.892677/full |
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